Chow L, Zakrzewska K, De Gasparo M, Cumin F, Levens N
Research Department, Pharmaceuticals Division, Ciba-Geigy Ltd, Basel, Switzerland.
Eur J Pharmacol. 1995 Dec 27;294(1):309-17. doi: 10.1016/0014-2999(95)00546-3.
This study tested the hypothesis that angiotensin II acting through the angiotensin AT1 receptor plays an important role in the control of gastric acid secretion. Basal gastric acid secretion and gastric blood flow were lower in Na(+)-depleted animals, in which the renin-angiotensin system was activated, than in animals maintained on a normal Na+ diet. Intravenous infusion of pentagastrin at 0.6 microgram/kg/min increased gastric acid secretion to a greater extent in normal Na+ than in Na(+)-depleted animals. In addition to stimulating gastric acid secretion, pentagastrin increased gastric blood flow by proportionally the same amount in both normal and low Na+ animals. However, because basal gastric blood flow was considerably reduced in Na(+)-depleted animals, the increase produced by pentagastrin extended only to the levels observed in non-pentagastrin-treated normal Na+ animals. Lower gastric blood flow in response to pentagastrin may explain the smaller increase in gastric acid secretion observed in Na(+)-depleted animals. In Na(+)-depleted animals, the selective angiotensin AT1 receptor antagonist losartan did not affect basal gastric acid secretion or gastric blood flow, suggesting the involvement of mechanisms other than angiotensin II. Following blockade of angiotensin AT1 receptors, pentagastrin significantly increased gastric blood flow in Na(+)-depleted animals to levels observed with infusion of the pentapeptide in normal Na+ animals. The results suggested that the decrease in pentagastrin-stimulated acid secretion in Na(+)-depleted animals is mediated by angiotensin II acting through the angiotensin AT1 receptor, most probably through vascular mechanisms.
通过血管紧张素AT1受体起作用的血管紧张素II在胃酸分泌的调控中起重要作用。肾素-血管紧张素系统被激活的低钠动物的基础胃酸分泌和胃血流量低于维持正常钠饮食的动物。以0.6微克/千克/分钟的速度静脉输注五肽胃泌素时,正常钠动物的胃酸分泌增加幅度大于低钠动物。除了刺激胃酸分泌外,五肽胃泌素使正常和低钠动物的胃血流量按比例增加相同幅度。然而,由于低钠动物的基础胃血流量显著降低,五肽胃泌素引起的增加仅达到未用五肽胃泌素处理的正常钠动物所观察到的水平。五肽胃泌素引起的胃血流量降低可能解释了低钠动物胃酸分泌增加幅度较小的原因。在低钠动物中,选择性血管紧张素AT1受体拮抗剂氯沙坦不影响基础胃酸分泌或胃血流量,提示存在血管紧张素II以外的机制参与。阻断血管紧张素AT1受体后,五肽胃泌素使低钠动物的胃血流量显著增加至正常钠动物输注五肽时所观察到的水平。结果表明,低钠动物中五肽胃泌素刺激的胃酸分泌减少是由通过血管紧张素AT1受体起作用的血管紧张素II介导的,很可能是通过血管机制。